Albumin, a small protein of about 5 nm diameter, which is in abundance in the blood, has a strong tendency to accumulate in tumors. Albumin has therefore been used as drug carrier, since it has a hydrophobic pocket that can encapsulate hydrophobic drugs.
Loading of a drug into albumin can occasionally be achieved by mixing the drug and carrier although this is often not the most promising approach. More commonly, the drug is conjugated to albumin using established procedures. A prodrug is conjugated to the protein—often via a cleavable peptide linker—using maleimides, isocyanates, N-hydroxysuccinimide esters and others. This approach has been applied to several drugs, among them doxorubicin, 5-fluorouracil and platinum (II).
The EPR (enhanced permeation and retention) effect of tumors however is more pronounced with particles well above the size of a single albumin molecule. Nanoparticles in the range above 20 nm are known to lodge in tumors but cannot readily be cleared from the site, leading to retention of the drug carrier in the tumor. Therefore, albumin has been converted into nano-sized particles via a precipitation process. In this process the drug functions to aggregate the molecules of albumin. As a result several hundred albumin molecules build up a particle with a size of more than 200 nm. The product is commonly known as nab-albumin and a version with paclitaxel has recently been marketed as Abraxane®.
A disadvantage of the nab-albumin technology is that it is not well suited to producing particles below 100 nm in diameter: the nature of the processing step does not favour the formation of smaller particles. However, it is known that for good lodgement in tumors, smaller particles are required. Additionally, the nab-albumin technology is not suitable for the use with a number of useful drugs such as genes, peptides and proteins.
There is therefore a need for an albumin-based product having particle size below 100 nm in diameter and capable of encapsulating a range of different drugs, preferably drugs capable of treating tumors.